Derivatives of isonicotinyl hydrazine



,ried out Ul'lltd sta 2,703,322 DERIVATIVES F ISONICOTINYL HYDRAZINE Herman Herbert Fox, Passaic, N. 1., assignor to Holfmann-La Roche Inc., Nutley, N. 1., a corporation of New Jersey No Drawing. Application March 17,

Serial No. 216,256

7 Claims. (Cl. 260-295) cycloalkylidene, furfurylidene or pyrimidylidene radical. e compounds can be represented by the followmg general formula:

wherein R has the same meaning already assigned thereto.

ong the substances which are included in this invention are straight chain alkylidene derivatives of isonicotinyl hydrazine, e. g., 1-isonicotinyl-Z-ethylidene hydrazine, l-isonicotinyl-2-propylidene hydrazine, l-isonicotinyl-Z- butylidene hydrazine, 1-isonicotinyl-Z-hexylidene hydrazine, 1-isonicotinyl -2- eptylidene hydrazine; hranched 1-isonicotinyl-2-isopropylidene hydrazine, l-isonicotinyl- 2-isobutylidene hydrazine, l-isonicotinyl-Z-(2-ethylhcxylidene) hydrazine, and l-isonicotinyl-2-(l-methylheptylidene) hydrazine; cycloalkylidene derivatives of isonicotinyl hydrazine, e. g., l-isonicotinyl-2-cyclohexylidene hydrazine; l-isonicotinyl-Z-(2,4,6-trioxo-hexahydro--pyrimidylidene) hydrazine; and l-isonicotinyl-Z-(Z-furfurylidene) hydrazine. The new compounds are useful to combat tuberculosis.

e new compounds can be prepared by reacting iso- Example 1 The Example 2 A mixture of 40 grams of isonicotinyl hydrazine and 600 cc. of acetone was heated on a steam bath until solution was complete. Upon cooling the reaction mixture, l-isonicotinyl-2-isopropylidene hydrazine precipitated in the form of white needles; M. P. 161-1615 C.

Example 3 Isonicotinyl hydrazine (21 grams) was dissolved in cc. of water, and 15 grams of cyclohexanone were added to the clear solution. The resulting two phase system was shaken until the cyclohexanone dissolved, upon which l-isonicotinyl-Z-cyclbhexylidene hydrazine egan to precipitate out in the form of white needles; M. P. 167.5169.5 C.

5 about minutes.

2,703,322 Patented Mar. 1', 1955 2 Example 4 A mixture of 40 grams of isonicotinyl hydrazine, 30 cc. of furfural and 200' cc. of methanol was refluxed -for The reaction mixture was cooled, and the fine white needles of 1-isonicotinyl-2-(Z-furfurylidene7)hy1drazine were filtered oil. The compound melted at 21 2 8 C.

Example 5 A mixture of 40 grams of isonicotinyl hydrazine, 50 cc. of methyl hexyl ketone and 300 cc. of methanol was refluxed for 4 hours. The methanol was removed under vacuum, and 200 cc. of ligroin (B. P. 60-90 C.) were added The mixture was heated on a steam bath, stirred and finally cooled, whereupon white needles of l-isonicotinyl-2-(l-methylheptylidene)hydrazine formed. The compound melted at 75-77 C.

Example 6 Isonicotinyl hydrazine (27.4 grams) in 375 cc. of water was mixed with 32 grams of alloxan in 160 cc. of

The white crystalline precipitate of l-isonicotinyl-2-(2,4,6-trioxohexahydro-S-pyrimidylidene) hydrazine which formed melted with decomposition at 243.5 C.

Example 7 Isonicotinyl hydrazine (40 grams),

40 cc. of butyraldehyde and 300 cc. of methanol were mixed.

vacuum Upon cooling, the residue crystallized. Rec stallization from toluene yielded white granular crystals of 1-isonicotinyl-2-butylidene hydrazine; 1l3- Example 9 Isonicotinyl hydrazine (20 grams), 18 grams of 2-ethylhexaldehyde and cc. of water were mixed, wh a two-phase oil-water system the oily phase formed a white precipitate of 1-isonicotinyl- 2 2 ethylhexylidene)hydrazine. On recrystallization from a mixture of ligroin (B. P. 60-90" C.) and xylene, the compound melted at 89.5-91.5 C.

Example 10 Isonicotinyl hydrazine 20 grams), 17 grams of heptaldehyde and 150 cc. of water were mixed whereupon a two-phase oil-water system was formed. On shaking, the oily phase formed a precipitate of l-isonicotinyl-Z-heptylidene hydrazine. On recrystallization from xylene, the compound melted at l0l102 C.

Example 11 grams of isonicotinyl hydrazine, 20 cc. f methanol was warmed to syrup was obtained which gave a white l-isonicotinyl-Z-hexylidene hydrazine on treatment with ether. On recrystallization from xylene, the compound melted at 121.5-123 C.

Example 12 To a warm solution of 20 grams of isonicotinyl hydrazine in 150 cc. of methanol were added 20 f isobutyraldehyde.

15 minutes.

aim: 1. 1-isonicotinyl-Z-R-hydrazines, wherein R is a member of the group consisting of a lower alkylide'ne, cyclohexylidene, furfuryliden'e, and 2,4,6-trioxo-hexahydro-pyrimidyiidene radical.

2. l-isonicotinyl-Z- lower alkylidene hydrazine.

3. 1-isonicotinyi-2-isopropylidene hydrazine.

4. l-isonicotinyI-Z-cyclohexylidene hydrazine.

5. 1isonicotinyl-Z-hexylidene hydrazine.

6. 1-isonicotinyl-2-isobuty1idene hydrazine.

7. l-isonictstinyl-Z-(z-e'thylhexylidene) hydrazine.

References Cited in 'the file of this patent 

1. 1-ISONICONTINYL-2-R-HYDRAZINES, WHEREIN R IS A MEMBER OF THE GROUP CONSISTING OF A LOWER ALKYLIDENE, CYCLOHEXYLIDENE, FURFURYLIDENE, AND 2, 4, 6-TRIOXO-HEXAHYDRO-PYRIMIDYLIDENE RADICAL. 